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Journal of Orthopaedics and Traumatology

Official Journal of the Italian Society of Orthopaedics and Traumatology

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The application of antibiotic-loaded bone cement in preventing periprosthetic joint infection: an umbrella review

Journal of Orthopaedics and Traumatology volume 26, Article number: 23 (2025) Cite this article

Abstract

Objectives

The purpose of this study was to provide thorough, understandable and precise evidence for the clinical use of antibiotic-loaded bone cement (ALBC) in preventing periprosthetic joint infection (PJI).

Methods

We evaluated the effectiveness of ALBC in preventing PJI by conducting an umbrella review of existing meta-analysis. Four databases, PubMed/MEDLINE, Cochrane Library, Embase and Web of Science, were searched until May 2024. Two reviewers were reviewers for literature screening, and data were extracted independently. AMSTAR 2 guideline and GRADE were also used for quality evaluation. The clinical outcomes were evaluated for effectiveness by several indicators, including surface infection rate (SIR), deep infection rate (DIR), total infection rate (TIR), unadjusted/adjusted all-cause revision rate, and revision rate for PJI.

Results

We synthesized the results of ten meta-analyses. Two meta-analyses had high AMSTAR 2 scores, two had moderate AMSTAR 2 ratings, three had critically low AMSTAR 2 scores, and the remaining meta-analyses had low AMSTAR 2 ratings. In terms of postoperative surgical site infection and revision rate, SIR (OR 1.50, 95% CI 1.14, 1.99, P = 0.004, I2 = 0%), unadjusted all-cause revision rate (RR 1.44, 95% CI 1.08, 1.90, P = 0.011, I2 = 91.8%) and adjusted all-cause revision rate (HR 1.21, 95% CI 1.12, 1.31, P < 0.001, I2 = 0%) in ALBC group were significantly higher than those in non-antibiotic-loaded bone cement (NALBC) group. ALBC group was significantly lower than NALBC group in DIR (OR 0.53, 95% CI 0.39, 0.70, P < 0.0001, I2 = 57%), (RR 0.506, 95% CI 0.341, 0.751, P = 0.001, I2 = 0%) and revision for PJI (RR 0.721, 95% CI 0.628, 0.828, P = 0, I2 = 53%). There was no statistical difference in total infection rate (TIR) between the ALBC group and the NALBC group (OR 0.81, 95% CI 0.51, 1.28, P = 0.37, I2 = 73%).

Conclusions

On the basis of the results of our analysis, we do not believe that ALBC is more effective than NALBC in preventing PJI after primary total joint arthroplasty (PTJA). No statistically significant difference was found on TIR between the two groups, although it was lower in the ALBC group. In addition, the DIR and revision for PJI are significantly lower in the ALBC group, but the results are of low quality, which calls for high-quality and large-sample studies in the future.

Highlights

  • This umbrella review included a total of ten meta-analyses.

  • The highest level of evidence to date suggests that antibiotic-loaded bone cement cannot be considered an effective prevention method for periprosthetic joint infection.

  • No statistically significant difference was found on TIR between the two groups, although it was lower in the ALBC group. In addition, the DIR and revision for PJI are significantly lower in the ALBC group, but the results are of low quality, which calls for high-quality and large-sample studies in the future.

Introduction

Periprosthetic joint infection (PJI), defined as an infection involving the joint prosthesis and adjacent tissues, is one of the most devastating and costly complications following total joint arthroplasty (TJA), and is the first and third cause of total knee arthroplasty (TKA) and total hip arthroplasty (THA) failure, respectively [1]. PJI, which affects 1.4–2.5% of total joint replacement patients worldwide, is associated with poor prognosis, reduced functional status, and prolonged hospital stays, requiring costly revision surgery [2, 3]. The economic burden of treating PJI is substantial, with estimated costs ranging from $60,000 to $100,000 per patient, excluding expenses related to surgery, additional healthcare services, and post-acute care [4]. Worse still, as life expectancy rises and the demand for joint replacement increases, the incidence of PJI will continue to grow [5]. Compounding this issue, some increasingly common systemic diseases, such as diabetes and obesity, are considered as significant risk factors for PJI [6]. However, there are still many shortcomings in the current treatments of PJI. Systemic antibiotic therapy is often ineffective in eradicating PJI due to impaired local blood circulation [7]. In addition, high doses of parenteral antibiotics can cause systemic toxicity and other adverse effects [8]. In addition, local antibiotic powder increases the incidence of incision complications [9]. Thus safer and more effective treatments for PJI are urgently needed.

Initially introduced by Buchholz et al. [10] in 1970, antibiotic-loaded bone cement (ALBC) is used to make beads and artificial joints by mixing bone cement powder with antibiotics in a specific proportion, and then placing them on the infected site of the human body. ALBC continuously elutes serum and inflammatory fluid, releasing high concentrations of local antibiotics, thus achieving the purpose of eliminating infection. In addition to providing mechanical fixation and support of traditional bone cement, ALBC offers the unique advantage of sustained local antibiotic release, making it a widely adopted strategy for preventing PJI in many countries [11]. However, the use of ALBC in joint replacement remains controversial. Turhan et al. indicated that ALBC did not reduce the incidence of deep infection in TKA compared with plain bone cement (PBC), emphasizing that bone cement without antibiotics was preferred [12]. However, in a large observational study, Jameson et al. showed that ALBC can significantly reduce the risk of revision for infection in TKA [13]. Parvizi et al. found a reduction in infection and revision rates in THA treated with ALBC, but we should be cautious because many nonrandomized trials were included [14]. In addition to uncertainty about its effectiveness in reducing postoperative infection rates, concerns have been raised about the mechanical stability, antibiotic resistance, and cost of ALBC [15]. According to the 2018 International Orthopaedic Infection Consensus, whether to recommend ALBC requires a high level of evidence to demonstrate its impact on surgical outcomes in patients with PJI [16].

Our hypothesis is that the preventive use of ALBC in patients undergoing joint replacement can significantly reduce the occurrence of postoperative PJI compared with NALBC, and improve the prognosis of patients by reducing revision surgeries. In this umbrella review, we comprehensively evaluated the methodological quality of relevant meta-analyses and observed the consistency of their evidence to provide comprehensive, understandable, and accurate evidence for the clinical use of ALBC in joint replacement.

Methods

An umbrella review evaluates and compiles data from various meta-analyses (MAs) on all outcomes, which can provide a broader understanding of many treatments than systematic reviews or meta-analyses limited to a comparison of one treatment or even one outcome [17, 18]. We used the procedures outlined in the Cochrane Handbook on conducting umbrella reviews [18,19,20]. Registered on the International Prospective Register of Systematic Reviews (PROSPERO) website, the work followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (PRISMA 2020 checklist) and A Measurement Tool to Assess systematic Reviews 2 (AMSTAR 2) Guidelines [21, 22].

Search methodology

Four databases were searched up to May 2024, including Cochrane Library, Embase, PubMed/MEDLINE, and Web of Science. The literature retrieval process involved using a combination of subject terms and free words to conduct the search [23]. The English search terms included “Prosthesis-Related Infections”, “Anti-Bacterial Agents”, “Bone Cements”, “Systematic review”, and “Meta-analysis”, etc. Specific search strategies can be found in Supplementary material A.

Study selection

Included criteria: follow the MAs or systematic reviews conducted by PRISMA [21]. The intervention group is ALBC MAs. MAs must comprise at least two trials in their outcome measures [24].

Exclusion criteria: conference abstracts, protocols, letters, and network MAs. Patients received a revision THA or TKA. The data are not accessible and appropriate. The article is not about ALBC versus NALBC treatment. The article is not retracted.

Overlapping discovery and processing

If two or more MAs contain the same outcome indicator, it is possible that the original studies included in them overlap. As a tool that can visually display overlap, Graphical Representation of Overlap for Overviews (GROOVE) was used to find where original research overlaps [25]. Using GROOVE, we can categorize overlap into four levels: very high (> 15%), high (10 to < 15%), moderate (5 to < 10%), and slight (< 5%). The results of GROOVE analysis are shown in Supplementary material D. When overlap occurs, the solution (overlapping solution, similarly hereinafter) is as follows [26, 27]: 1. If there are Cochrane reviews and non-Cochrane reviews with high or very high overlap (≥ 10%), the results of the Cochrane reviews are given priority. 2. If a high degree of overlap (≥ 10%) is found between two or more non-Cochrane reviews, the results of the meta-analysis with the highest AMSTAR 2 score are preferred. If the AMSTAR 2 scores were consistent, the results of the meta-analysis with the most randomized controlled trial (RCT) studies included or the most recent publication were given priority. 3. If slight or moderate overlap (< 10%) is found, all MAs are included.

Obtaining data and evaluating its quality

Two authors independently retrieve the data and assess its quality, and if disagreements arise, a third author will assist in resolving them. The main results extracted in this study include: superficial infection rate, deep infection rate, total infection rate, all-cause revision, and revision for PJI. The male ratio of included studies, average age, number of included RCT studies, number of arthroplasties in ALBC and NALBC groups undergoing total joint replacement, surgery of included MAs, and outcome indicators were also extracted. The authors independently assessed the methodological quality of the included MAs using AMSTAR 2. When there was a dispute, the senior author mediated to reach a consensus [28]. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) [29], the level of evidence for each outcome was assessed and divided into four categories: high, moderate, low, and very low. In addition, on the basis of evidence classification criteria, we also classified the resulting evidence into four categories: I (convincing evidence), II (highly suggestive evidence), III (suggestive evidence), IV (weak evidence), and NS (not significant). Detailed criteria for classification of evidence are presented in Table 1 [17].

Table 1 Evidence classification criteria
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Data synthesis

Systematic reviews and meta-analyses that met the inclusion criteria formed the unit of analysis. The results of the meta-analysis were pooled using 95% CI I2 and effect measures (RR, OR, etc.). Heterogeneity between studies was represented by I2, but an I2 > 50% indicated high heterogeneity and an I2 > 75% indicated very high heterogeneity, which may affect the uncertainty of the synthesis effect and the stability of the reported results [30]. The results obtained from reviews were combined using a narrative synthesis, with findings presented in a tabular format for reviews that conducted a meta-analysis (Supplementary material E). Summary tables describing review characteristics and findings were also presented.

Results

Search results

According to the search method, 85 studies were initially retrieved, of which 8 were excluded after removing duplicates, and 51 were carefully excluded according to the inclusion and exclusion criteria when reading the title and abstract. Finally, after reading the full text, 16 studies were excluded (Supplementary material B) and 10 systematic reviews were finally included. Figure 1 depicts the literature screening process.

Fig. 1
figure 1

Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) flow diagram to show study selection

Full size image

Study characteristics

Table 2 lists the basic characteristics of MAs included in this study. The MAs included in this review were issued between 2008 and 2024. Six studies studied primary TJA (primary THA and primary TKA included) [8, 31,32,33,34,35], one study only studied PTHA [14], and the remaining studies only studied PTKA [36,37,38]. The five MAs included fewer than ten studies [8, 31, 33, 34, 38]. The remaining five MAs included ten or more studies [14, 32, 35,36,37]. Among them, 1 study included 30 or more studies. Four studies provided specific sex ratios [31, 35, 37, 38]. Six studies provided the average age of the patients [8, 31, 35,36,37,38]. Nine studies provided a range of follow-up times [8, 31,32,33,34,35,36,37,38]. The main conclusions from all included studies were extracted in this review as presented in Table 3. The overall ratings of the quality evaluation of each MAs were added in Table 2, and the specific details were provided in Supplementary material C. Two MAs have a high AMSTAR 2 rating [32, 36], two have a moderate AMSTAR 2 rating [8, 37], and three have a low AMSTAR 2 rating [31, 33, 35]. The remaining three MAs have critically low AMSTAR 2 ratings [14, 34, 38].

Table 2 Basic information about study patients was included
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Table 3 Main conclusions of the study are included
Full size table

Results of umbrella review

Superficial infection rate

A total of three MAs reported SIR [8, 32, 38]. One study had a high AMSTAR 2 score [32], one was moderate [8], and one was critically low [38]. The overlap of these three MAs was identified using the GROOVE tool, as shown in Supplementary material D. On the basis of the overlapping solution, the results of Jin Zhang et al.’s study [32] are considered to represent the best available evidence. The results showed that SIR in ALBC group was significantly higher than that in NALBC group (OR 1.50, 95% CI 1.14, 1.99, P = 0.004, I2 = 0%). The results were graded as moderate and the evidence level was: IV (Supplementary material E).

Deep infection rate

A total of five MAs reported DIR [8, 14, 32, 34, 38]. Three studies had critically low AMSTAR 2 scores [14, 34, 38], one was moderate [8], and one was high [32]. The overlap of these five MAs was identified using the GROOVE tool, as shown in Supplementary material D. On the basis of the overlapping solution, the results of Jin Zhang et al. [32], and Parvizi et al. [14] are considered to represent the best available evidence. Jin Zhang et al.’s [32] results showed that DIR in the ALBC group was significantly lower than that in the NALBC group (OR 0.53, 95% CI 0.39, 0.70, P < 0.0001, I2 = 57%). The results were rated at very low GRADE and evidence level: III (Supplementary material E). Parvizi et al.’s [14] research results showed that DIR in the ALBC group was significantly lower than that in the NALBC group (RR 0.506, 95% CI 0.341,0.751, P = 0.001, I2 = 0%). The results were graded low and the evidence level was III (Supplementary material E).

Total infection rate

A total of seven MAs reported TIR [8, 31,32,33, 36,37,38]. Two of the studies had high AMSTAR 2 scores [32, 36], two had moderate scores [8, 37], two had low scores [33, 38], and one had critically low scores [38]. The overlap of these seven MAs was identified using the GROOVE tool, as shown in Supplementary material D. On the basis of the overlapping solution, the results of Jin Zhang et al.’s study [32] are considered to represent the best available evidence. The results showed that TIR in the ALBC group was lower than that in the NALBC group (OR 0.81, 95% CI 0.51, 1.28, P = 0.37, I2 = 73%). The results were graded very low and the evidence level was NS (Supplementary material E).

Unadjusted all-cause revision rate

A total of two MAs reported unadjusted all-cause revision rates. One study had a moderate AMSTAR 2 score [37] and the other had a low score [35]. The GROOVE tool was used to identify the overlap between these two MAs, as shown in Supplementary material D. On the basis of the overlapping solution, it is considered that the results of Hao-Qian Li et al.’s study [37] represent the best available evidence. The results showed that the unadjusted all-cause revision rate in the ALBC group was significantly higher than that in the NALBC group (RR 1.44, 95% CI 1.08, 1.90, P = 0.011, I2 = 91.8%). The results were rated at very low GRADE level and evidence level: IV (Supplementary material E).

Adjusted all-cause revision rate

A total of two MAs reported adjusted all-cause revision rates. One study had a moderate AMSTAR 2 score [37] and the other had a low score [35]. The GROOVE tool was used to identify the overlap between these two MAs, as shown in Supplementary material D. On the basis of the overlapping solution, it is considered that the results of Hao-Qian Li et al.’s study [37] represent the best available evidence. The results showed that the adjusted all-cause revision rate in the ALBC group was significantly higher than that in the NALBC group (HR 1.21, 95% CI 1.12, 1.31, P < 0.001, I2 = 0%). The results were rated at very low GRADE and evidence level: III (Supplementary material E).

Revision for PJI

A total of two MAs reported revisions for PJI. One study had a low AMSTAR 2 score [35] and the other had a critically low score [14]. The GROOVE tool was used to identify the overlap between these two MAs, as shown in Supplementary material D. On the basis of the overlapping solution, the results of Farhan-Alanie et al. [35] and Parvizi et al. [14] are considered to represent the best available evidence. Farhan-Alanie et al.’s [35] results showed that revision for PJI in the ALBC group was lower than that in the NALBC group (RR 0.81, 95% CI 0.62, 1.08, P = 0.15, I2 = 80%). The results were graded low and the evidence level was NS. (Supplementary material D). Parvizi et al.’s [14] research results showed that revision for PJI in the ALBC group was significantly lower than that in the NALBC group (RR 0.721, 95% CI 0.628, 0.828, P = 0, I2 = 53%). The results were graded low and evidence level: II (Supplementary material E).

Discussion

PJI is a global healthcare challenge that necessitates the exploration of effective treatment to improve patient outcomes and alleviate the economic burden on healthcare systems. There have been multiple studies investigating the preventive effect of ALBC in reducing PJI [39,40,41], but the efficacy of ALBC remains a controversial issue. Therefore, it is necessary to conduct an umbrella review on the effectiveness of ALBC.

The main results of this study were that, following joint replacement, the SIR, unadjusted all-cause revision rate and adjusted all-cause revision rate in the ALBC group were significantly higher than those in the NALBC group. However, the ALBC group was significantly lower than the NALBC group in DIR and revision for PJI despite low-grade evidence. There was no statistical difference in TIR between the ALBC group and the NALBC group.

ALBC serves not only as a joint fixation, but also as a carrier of antibiotics, delivering them directly to the site that has been or is about to be infected. Additionally, the release of antibiotics from ALBC followed a biphasic pattern, characterized by an initial peak release followed by a prolonged, low-level release lasting days to months [42]. This sustained release mechanism may account for the low DIR and revision for PJI in the ALBC group. According to the results, ALBC was less effective in reducing SIR compared with systemic antibiotics. This is likely due to diminished concentrations in areas farther from the ALBC, which may fail to inhibit or eliminate the bacteria at the superficial incision site [32]. In spite of the decrease of revision for PJI in the ALBC group, the unadjusted and adjusted all-cause revision rate were higher than those in the control group. This discrepancy may stem from ALBC’s potential adverse effects on the physical properties of bone cement, so that the reduction of revision for PJI cannot offset the revision caused by other problems [35]. The high heterogeneity observed in some outcomes may be attributed to differences in study design, time and district of the study implemented, duration of follow-up, types of antibiotics used in ALBC, operating room conditions, or systemic antibiotic use.

The results of this study were compared with those of other studies. A meta-analysis conducted by King et al. showed that ALBC did not reduce the prevalence of PJI compared with PBC [41]. Similarly, a review by Schiavone Panni et al. showed that patients receiving ALBC found no significant difference in the incidence of deep or superficial surgical site infections during PTKA compared with the control group (plain bone cement) [43]. In addition, a recent registry-based meta-analysis showed that the risk of PJI revision for ALBC after PTKA was similar to that for conventional bone cement [39]. More interestingly, no statistically significant difference in PJI rates was found between cemented and cementless straight-stem prostheses, with the latter demonstrating superior survivorship and functional outcomes [44, 45]. In contrast, according to a meta-analysis by Sebastian et al., ALBC has potential in reducing the risk of infection after primary hip or knee replacement [33]. However, the applicability of this finding is limited, as most of the nine RCTs included in the meta-analysis were conducted more than 19 years ago, raising questions about their relevance to the current joint replacement standards. Additionally, a retrospective cohort study based on Catalan Arthroplasty Register showed lower septic and aseptic revision rates after TKA in ALBC group, but the results may be biased due to unexplored confounders and inputted values for the missing values of some available confounders [40]. Rodriguez-Merchan et al. advise that caution in the use of ALBC is recommended, but may only be appropriate for patients at high risk of infection, such as those with compromised immune function, morbid obesity, or diabetes [46].

In addition to the above outcome indicators, the incidence of acute kidney injury (AKI) is another critical consideration in the application of ALBC. A review of ten observational studies by Luu et al. reported a 4.8% incidence of AKI associated with antibiotic spacers [47]. Furthermore, A recent meta-analysis of 2525 patients with PJI revealed that the incidence of AKI in patients using ALBC was 16.6%, with 1.4% requiring acute dialysis [48]. Although it is uncommon for patients with AKI to require acute dialysis, the potential progression to chronic kidney disease necessitates careful evaluation.

Another concern is the cost of ALBC. In the case that the efficacy of ALBC is not better than PBC, choosing ALBC is not a cost-effective choice, as ALBC is 3–5 times more expensive than PBC. King et al. argue that ALBC is an unnecessary cost to the healthcare system, and that a hospital system performing 1000 TKAs per year could save $155,000 to $310,000 per year by switching to regular cement [41]. In addition, calculations by Yayac et al. revealed that ALBC would add $229 per person to clinical care, with no decrease in the PJI rate [49]. In addition, the application of ALBC is associated with increased hospitalization costs, average surgical time, and length of stay, which has been widely accepted by surgeons [37]. Pellegrini et al., however, emphasize that the cost of treatment for high-risk patients (e.g., obesity, diabetes) could indeed benefit from budgetary expenditures for ALBC [50].

This umbrella review provides a comprehensive analysis of the effectiveness of ALBC in preventing PJI, and represents the most extensive synthesis of evidence in this field to date. However, this umbrella review has several limitations: individual MA has inherent selection, reporting, and publication bias. This umbrella review is restricted to English language MAs, excluding non-English publications. In addition, more than half of the MAs included in this study had low or critically low AMSTAR 2 scores, which may affect the credibility of the results. Many MAs did not provide more detailed population characteristics (such as age, systemic disease), which limits the ability to generalize findings to specific patient subgroups. To address these limitations, future research should focus on conducting high-quality and large-scale studies with rigorous methodologies to minimize bias and improve the reliability of the evidence. Special attention should be given to high-risk patient populations, such as those with diabetes and obesity, to further determine whether ALBC is a cost-effective approach. However, the efficacy of ALBC in these patient subgroups necessitates additional RCTs for robust validation.

Conclusions

On the basis of the results of our analysis, we do not believe that ALBC is more effective than NALBC in preventing PJI after PTJA. No statistically significant difference was found on TIR between the two groups, although it was lower in the ALBC group. In addition, the DIR and revision for PJI are significantly lower in the ALBC group, but the results are of low quality, which calls for high-quality and large-sample studies in the future.

What is already known on this topic?

PJI is one of the most serious complications after total joint replacement and is closely associated with poor postoperative prognosis. It affects 1.4–2.5% of total joint replacement patients and its incidence will increase. ALBC is widely used worldwide to prevent PJI, but its efficacy has been controversial.

What this study adds?

This study explored the use of ALBC in the prevention of PJI after total joint replacement from the aspects of efficacy, postoperative complications, cost performance, etc., and put forward unsupported views. The study highlights the need for future large-scale randomized controlled clinical studies to determine the efficacy of ALBC in preventing PJI.

Availability of data and materials

The data that support the findings of this study are available on request from the corresponding author, upon reasonable request and with the provision of a data sharing agreement.

Abbreviations

ALBC:

Antibiotic-loaded bone cement

PJI:

Periprosthetic joint infection

SIR:

Superficial infection rate

DIR:

Deep infection rate

TIR:

Total infection rate

PTJA:

Primary total joint arthroplasty

PTKA:

Primary total knee arthroplasty

PTHA:

Primary total hip arthroplasty

AKI:

Acute kidney injury

PBC:

Plain bone cement

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Acknowledgements

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Funding

This work was supported by National Key R&D Program of China (no. 2023YFB4606705), National Natural Science Foundation of China (no. 82272611, 82472522, 82072506, 92268115), Hunan Provincial Science Fund for Distinguished Young Scholars (no. 2024JJ2089), Science and Technology Innovation Program of Hunan Province (no. 2023SK2024), Natural Science Foundation of Hunan Province (2023JJ30949), and Shaanxi Province Technology Committee Project (no. 2021JM576).

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  1. Yangbin Cao and Peiyuan Tang contributed equally.

Authors and Affiliations

  1. Department of Orthopedics, Xiangya Hospital, Central South University, Hunan, China

    Yangbin Cao, Peiyuan Tang, Ahmed Abdirahman, Wenfeng Xiao, Yusheng Li & Ting Wen

  2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China

    Peiyuan Tang, Ahmed Abdirahman, Wenfeng Xiao, Yusheng Li & Ting Wen

  3. Xiangya School of Medicine, Central South University, Changsha, China

    Yangbin Cao, Hua Chai, Wenbo Ma, Bin Lin & Ying Zhu

  4. The First People’s Hospital of Changde City, Changde Hospital, Xiangya Medical College, Central South University, Changsha, 415000, China

    Jun Zhang

  5. Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Shuguang Liu

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Cao, Y., Tang, P., Chai, H. et al. The application of antibiotic-loaded bone cement in preventing periprosthetic joint infection: an umbrella review. J Orthop Traumatol 26, 23 (2025). https://doi.org/10.1186/s10195-025-00839-w

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